Dry powder formulation of kanamycin with enhanced aerosolization efficiency for drug-resistant tuberculosis

• Published in: International journal of pharmaceutics 2017-08, Vol.528 (1-2), p.107-117
• Main Authors: Momin, Mohammad A.M., Sinha, Shubhra, Tucker, Ian G., Doyle, Colin, Das, Shyamal C.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosols; Cell Line, Tumor; Dry powder inhaler; Dry Powder Inhalers; Humans; Hygroscopic; Kanamycin; Kanamycin - administration & dosage; l-leucine; Particle Size; Powders; Spray-drying; Tuberculosis; Tuberculosis, Multidrug-Resistant - drug therapy
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2017.06.004

[Display omitted] Kanamycin, an injectable agent, is currently used to treat drug-resistant tuberculosis (TB). Parenteral kanamycin causes high systemic toxicity which could be avoided by direct delivery to the lungs. This study focused on producing a highly aerosolizable dry-powder of hygroscopic kanamycin by spray-drying with l-leucine. Kanamycin powders were prepared with different concentrations (0, 5, 10, 15 and 20% w/w) of l-leucine using the Buchi B-290 Mini Spray-Dryer. In vitro aerosolization efficiency, particle size, morphology, crystallinity, surface composition, drug-excipient interaction and moisture content of the powders were characterized by a Next Generation Impactor (NGI), laser diffraction, scanning electron microscopy, X-ray diffractometry, XPS, ATR-FTIR and thermogravimetric analysis. The physicochemical and aerosolization stability of the powders were investigated after one-month storage at 25±2°C/15% RH and 25±2°C/75% RH. The cytotoxicity on Calu-3 and A549 cells of the kanamycin powders was evaluated by MTT assay. The spray-dried powder particles were in the inhalable size range (